The etiology of cancer is extremely complex, and remains poorly understood. What is known is that cancers are intimately related to both environmental factors as well as internal factors of the human body. About three quarters of cancers can be attributed to external, environmental causes. Cancers continue to pose great threat to humanity, and worldwide at least 5 million people die from cancer annually. Currently available methods of treatment, such as surgery, radiotherapy, chemotherapy all have their limitations.
Of the available cancer treatment and prevention methods, chemical agents remain the most effective.
One category of cancer chemotherapy agents are the inhibitors or antagonists of both receptor tyrosine kinases and non-receptor tyrosine kinases. Specific targets include vescular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), HER2 (human epidermal growth factor receptor 2), SRC, JAK (Janus kinase) and TEK.
Certain thieno-pyridazine compounds have been found to have anti-tumor activities. For example, WO2005105808 discloses such a compound as an IKK inhibitor:
In addition, WO2007124181 discloses compounds that are inhibitors of p38 protease, a type of tyrosine kinase:
Further, WO 03029241, WO 03028731 and WO2005066163 disclose similar compounds that are inhibitors of CHK1.
Nevertheless, there is a need for more anti-cancer compounds that are inhibitors of tyrosine kinases, especially CHK1/CHK2.